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Interleukin (IL) 10 looms as a highly promising treatment for rheumatoid arthritis (RA) because of its capacity to inhibit cellular immunity and deactivate macrophages. In RA, activated CD4 T helper cells and macrophages are believed to be the primary driving force behind joint inflammation. Synovial macrophages play a critical part in stimulating synovial inflammation. They produce abundant quantities of pro-inflammatory cytokines such as IL1 and tumour necrosis factor (TNF) α. The body attempts to keep the inflammatory response in check by upregulating the synthesis of endogenous inhibitors such as IL1 receptor antagonist (ra), soluble TNF receptors (TNFR), and IL10. These inhibitors act in concert to dampen the inflammatory response. IL10 is relatively unique in its ability to downregulate the production of multiple pro-inflammatory cytokines, leading to the notion that IL10 would be an effective treatment for RA.
Biology of IL10
Monocytes and macrophages produce IL10 when they are activated with the bacterial endotoxin lipopolysaccharide (LPS). There is an initial burst of pro-inflammatory cytokines (TNFα, IL1, IL6, and GM-CSF) followed later by a rise in IL10 synthesis.1 LPS stimulated IL10 production requires both the synthesis of TNFα and IL1 as well as cognate interactions between monocytes and T cells.2 ,3 IL10 release from LPS stimulated monocytes may be increased by transforming growth factor (TGF) β, interferon (IFN) α, IFNβ,4-6 histamine7 and ligation of the Fcγ receptor I.8 On the other hand, LPS stimulated IL10 production may be inhibited by IL4, IFNγ,9 ,10 and ligation of CD23, the low affinity IgE receptor.11 IL10 and IL12 appear to be coordinately regulated in many of these experimental systems such that IL12 upregulates the synthesis of IL10 that controls the extent of the response.7 ,8
T cells also produce IL10. This cytokine is a component of the …